CEFIXIME

Description: Antibacterial; β-lactam antibiotic; third generation cephalosporin.

Class: Third Generation Cephalosporins. United States Brands: Suprax. Chemical Name: [6R-[6α,7β(Z)]]-7-[[(2-Amino-4-thiazoyl)[(carboxymethoxy)imino]acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Cefixime in the treatment of respiratory and urinary tract infections. Cefixime is quickly establishing in

Western countries as a potent broad-spectrum antibiotic with a variety of indications. A multinational, nonrandomized study in Central and Eastern Europe has confirmed the excellent efficacy of cefixime in both children and adults. In 45 children with acute sinusitis and 50 with acute otitis media, once-daily cefixime in oral suspension resulted in clinical cure or improvement in 45 (100%) and 48 (96%) patients, respectively. In 60 adult patients with acute exacerbations of chronic bronchitis and 12 with pneumonia, cefixime 400 mg resulted in cure or improvement in 59 (98%) and 12 (100%) patients, respectively. Similarly, excellent efficacy was found in adults with urinary tract infections (UTI), with cure in 80 (94%) patients

Cefixime the first oral third-generation cephalosporin.

In the early 1980's parenteral third generation cephalosporins changed the hospital use of antibiotics. The MICs of these cephalosporins are several dozen times lower than those of first or second generation cephalosporins for Enterobacteriaceae and they are much more beta-lactamase stable than second generation cephalosporins. After years of research, is has finally been possible to develop orally active compounds possessing the same antibacterial activity as parenteral third generation cephalosporins, either through the use of prodrugs, or by modifying the molecular structure of drugs. Cefixime is an example of the latter. The vinyl group at the 3-position of the cephem nucleus is responsible for the intestinal absorption of the intact molecule, primarily by a carrier-mediated transport mechanism. The aminothiazole ring and the R-oxyimino group on the side-chain at the 7-position are associated with an antibacterial activity similar to that of third generation cephalosporins. Thousands of adults have been treated by cefixime for lower respiratory tract, ear-nose-throat and urinary tract infections, showing that cefixime is a safe and effective antimicrobial agent. The major clinical indications for cefixime in adults are bronchial and pulmonary infections, acute otitis or sinusitis, acute pyelonephritis with no underlying uropathy, and complicated or uncomplicated lower urinary tract infections excluding prostatitis. In all cases, the dosage is 200 mg b.i.d.

Cefixime

The β-lactam ring is crucial to the mechanism.

The carboxylic acid at position 4 is important to bind .

The bicyclic syastem is important in increaseing ring strain.

Stereochemistry is important. The acetoxymethyl substituent is important

to the mechanism.

Possible modifications: 3-Acetoxymethyl side chain. Substitution at C-7.

NOTE:

Structure-activity relationship of oral cephalosporins.

The advances achieved in the field of oral cephalosporins consist of improved bioavailability and enhanced intrinsic activity of the compounds. Oral absorption is facilitated either by creating prodrugs or by modifying the compound itself with addition of the alpha-amino group at position 7 on the cephem ring or of a vinyl group at position 3. Antibacterial activity and resistance to beta-lactamases are facilitated by the presence of an amino-2-thiazole heterocycle at position 7, associated with a methoxy-imino group or an oxy-imino-acetoxy group

Clinical role of Cefixime in communityacquired infections.

THE AIM:

of this study was to evaluate the efficacy of cefixime in the treatment of community-acquired infections in a country where parenteral third generation cephalosporins have been used for a long time. The present study was designed to assess the clinical efficacy, bacteriological eradication rates and tolerability of cefixime in children with community-acquired upper RTI (URTI), lower RTI (LRTI) and uncomplicated urinary tract infections (UTI).

MATERIALS AND METHODS:

The study was prospective, open, and included 89 patients, from 6 months to 28 years, of both sexes, with the diagnosis of community-acquired URTI, LRTI and UTI.

A review of the safety profile of cefixime.

Data are reviewed for safety from worldwide clinical trials of 4000 patients and postmarketing studies of 38,000 patients treated with cefixime, a broad-spectrum, bactericidal, beta-lactam stable, third-generation cephalosporin. Adverse experiences were similar in adults and children in all groups, with the most frequent side effects being gastrointestinal in nature.

Based on spectrum of activity, classified as a third generation cephalosporin. Expanded spectrum of activity against gram-negative bacteria compared with first and second generation cephalosporins; less active against Enterobacteriaceae than some other third-generation cephalosporins.

Usually bactericidal. Like other β-lactam antibiotics,

antibacterial activity results from inhibition of bacterial cell wall synthesis.

Spectrum of activity includes many gram-positive and gram-negative aerobic bacteria; inactive against most anaerobic bacteria. Inactive against chlamydia, fungi, and viruses.

Gram-positive aerobes: Active in vitro and in clinical infections against Streptococcus pneumoniae1 and Streptococcus pyogenes (group A β-hemolytic streptococci). Also active in vitro against S. agalactiae (group B streptococci) and groups C, F, and G streptococci.

ACTION:

Most staphylococci, enterococci, and Listeria monocytogenes are resistant.

Strains of staphylococci resistant to penicillinase-resistant penicillins (oxacillin-resistant [methicillin-resistant] staphylococci) should be considered resistant to cefixime, although results of in vitro susceptibility tests may indicate susceptibility.

Gram-negative aerobes: Active in vitro and in clinical infections against Neisseria gonorrhoeae, Haemophilus influenzae (including β-lactamase-producing strains),  Moraxella catarrhalis (including β-lactamase-producing strains), Escherichia coli, and Proteus mirabilis. Also active in vitro against H. parainfluenzae, Klebsiella, Pasteurella multocida, P. vulgaris, Providencia, Salmonella, Shigella, and Serratia. Most Enterobacter and Pseudomonas are resistant.